Mechanisms involved in chylomicron remnant lipid uptake by macrophages
Mechanisms involved in chylomicron remnant lipid uptake by macrophages
复制标题
DOI：
10.1042/bst0350459
复制
发表时间：
2007-06-01
影响因子：
3.9
通讯作者：
Napolitano, M.
中科院分区：
文献类型：
--
作者：
Bravo, E.;Napolitano, M.
尽管乳糜微粒残留物很明显会导致动脉粥样硬化，但导致其被巨噬细胞内化的事件仍然存在争议。 CRLP（乳糜微粒残留物样颗粒）中缺乏 apoE（载脂蛋白 E），可使巨噬细胞 TAG（三酰甘油）含量减少约 10%。 50%，表明除了 apoE 介导的内吞摄取外，apoE 受体独立机制也参与了乳糜微粒残余物诱导泡沫细胞的过程。与含有放射性标记脂质的 CRLP 一起孵育后与巨噬细胞相关的放射性评估表明，颗粒携带的 TAG 和胆固醇具有不同的内化动力学。此外，基于抑制的实验表明，胆固醇酯选择性摄取和TAG的细胞外脂蛋白脂肪酶水解分别有助于胆固醇和TAG积累。因此，血浆TAG和残余颗粒携带的胆固醇必须被视为动脉粥样硬化相关疾病的两个独立且不可互换的危险因素。此外，CRLP 和巨噬细胞之间的相互作用受到饮食氧化脂质和其他亲脂性成分的调节。 CRLP 中氧化脂质的存在，例如 7β-羟基胆固醇和 7-氧代胆固醇（动脉粥样硬化病变中发现的主要胆固醇氧化产物），会干扰其内化机制，但不会引起脂质积累的数量变化，而植物类胡萝卜素、番茄红素或抗氧化药物普罗布考的存在，通过增加颗粒的摄取率和提高脂质在巨噬细胞中的积累，从而增强巨噬细胞中的脂质积累。细胞内合成TAG。总之，有几种机制有助于巨噬细胞摄取餐后脂蛋白，然而，人们对不同途径之间的平衡和调节知之甚少。
Although it is clear that chylomicron remnants are atherogenic, events leading to their internalization by macrophages are still debated. The lack of apoE (apolipoprotein E) in CRLPs (chylomicron remnant-like particles) reduces macrophage TAG (triacylglycerol) content by approx. 50%, suggesting that, as well as apoE-mediated endocytic uptake, apoE receptor-independent mechanisms are involved in the induction of foam cells by chylomicron remnants. Evaluation of the radioactivity associated with macrophages after incubation with CRLPs containing radiolabelled lipids suggests that the TAG and cholesterol carried by the particles have different kinetics of internalization. In addition, inhibition-based experiments indicate that cholesteryl ester-selective uptake and the extracellular lipoprotein lipase hydrolysis of TAG contribute to cholesterol and TAG accumulation respectively. Thus plasma TAG and cholesterol carried by remnant particles have to be considered two independent and non-interchangeable risk factors for athero-related diseases. in addition, the interaction between CRLPs and macrophages is modulated by dietary oxidized lipids and other lipophilic components. The presence of oxidized lipids, such as 7 beta-hydroxycholesterol and 7-oxocholesterol, the major cholesterol oxidation products found in atherosclerotic lesions, in CRLPs interferes with the mechanisms of their internalization, but does not cause quantitative changes of accumulated lipids, while the presence of the plant carotenoid, lycopene, or the antioxidant drug, probucol, enhances lipid accumulation in macrophages by increasing the rate of uptake of the particles and raising the intracellular synthesis of TAG. in conclusion, several mechanisms contribute to the macrophage uptake of postprandial lipoproteins, however, little is known of the balance and modulation between the different pathways.,